2009B12 Discuss the production and function of red blood cells.







RBC structure:


   Biconcave disc shaped cell in blood

   8 x 2 μm


   Large amounts of haemoglobin, carbonic anhydrase, glycolytic enzymes

   No nucleus, no mitochondria (no aerobic metabolism)





   Yolk sac: early embryo

   Liver, spleen: embryo and foetus

   Appendicular skeleton: late foetus until adolescence

   Axial skeletal and proximal long bones: late foetus until death


   Erythopoietin (Epo) most important (see below)

   Colony stimulating factors (G-CSF, GM-CSF)

   Stem-cell factor


   Interleukins (esp. IL-3)

   With maturation: organelles disappear, [Hb] increases

   Circulating cells: 99% erythrocytes, 1% reticulocytes (reticular network of rRNA)


   Glycoprotein hormone

   Production: 90% renal interstitial fibroblasts, 10% liver (Fetus: mostly liver)

   Stimulus: cellular ↓pO2

   Mechanism: binds extracellular EpoR -> activates JAK2 cascade

   Effect: pluripotent cell -> erythroblast

   Degradation: liver



O2 carriage

   Fe2+ in haem binds O2

   Increases CaO2 from 2mL/100mL arterial blood (dissolved only) to 20mL/100mL

   O2 taken up at lungs (left shift OHDC: ↓H+, ↓pCO2, ↓T, ↓2,3-DPG)

   O2 unloaded at tissues (right shift OHDC: opposite)

   Used for oxidative phosphorylation, ATP production

Oxyhaemoglobin dissociation curve (OHDC)

CO2 carriage

   CO2 produced in TCA cycle

   Diffuses into RBC

   Converted by carbonic anhydrase and buffered

o  CO2 + H2O <-> H+ + HCO3-

o  CO2 + NH2 <-> NHCOO- + H+

o  KHb + H+ <-> HHb + K+

   Haldane effect: deoxyHb carries more CO2 and H+ than oxyHb

o  70% due to 3.5x↑ formation of carbamino

o  30% due to pKa 6.6 -> 8.2 imidazoles

o  Hence isohydric buffering: for every 1mol O2 offloaded, 0.7mol CO2 and H+ can be added, before pH falls

o  Note arterial pH 7.44, venous only 7.36 despite extra 4mL/100mL CO2


   Haemoglobin is the second most important ECF buffer after bicarbonate

   Effective in metabolic >> respiratory disorders

   As described above

Prevent nephrotoxicity

   Free haemoglobin damages the glomerulus



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